Seth Nicholson was born in Springfield, Illinois and raised on a farm in northern Illinois. He became interested in astronomy as an undergraduate at Drake University. As a graduate student at the University of California he was photographing the recently-discovered eighth moon of Jupiter with the 36-inch Crossley reflector when he discovered a ninth. He computed its orbit for his Ph.D. dissertation. At Mt. Wilson Observatory, where he spent his entire career, he discovered three more Jovian satellites, as well as a Trojan asteroid, and computed orbits of several comets and of Pluto. His main assignment at Mt. Wilson was observing the sun with the 150-foot solar tower telescope, and he produced annual reports on sunspot activity and magnetism for decades. He and Edison Pettit used a vacuum thermocouple to measure the temperatures of the moon, planets, sunspots, and stars in the early 1920s. Their temperatures measurements of nearby giant stars led to some of the first determinations of stellar diameters. Nicholson also made a number of eclipse expeditions to measure the brightness and temperature of the solar corona. He served as editor of the Publications of the Astronomical Society of the Pacific from 1943 to 1955.